Enomoto Masaru, Ikura Yoshihiro, Tamori Akihiro, Kozuka Ritsuzo, Motoyama Hiroyuki, Kawamura Etsushi, Hagihara Atsushi, Fujii Hideki, Uchida-Kobayashi Sawako, Morikawa Hiroyasu, Murakami Yoshiki, Kawada Norifumi
Department of Hepatology, Osaka City University Medical School, Osaka, Japan.
Department of Pathology, Takatsuki General Hospital, Takatsuki, Japan.
United European Gastroenterol J. 2018 Nov;6(9):1391-1400. doi: 10.1177/2050640618791053. Epub 2018 Jul 19.
Interferon-free, direct-acting antiviral treatments can result in a sustained virologic response in nearly 100% of patients with chronic hepatitis C virus infection.
The purpose of this study was to evaluate histological improvement after achieving a sustained virologic response to direct-acting antiviral treatments in patients with chronic hepatitis C.
Among 691 patients with chronic hepatitis C who achieved a sustained virologic response to direct-acting antivirals, 51 underwent liver biopsy 41 ± 20 weeks after the end of treatment despite normal transaminase levels. In 20 patients, liver biopsy specimens obtained a median of 1.2 years before the start of treatment were available.
Among the 51 patients who underwent post-sustained virologic response biopsies, the grade of inflammation was A0 in 18 patients, A1 in 24, A2 in eight, and A3 in one; the stage of fibrosis was F0 in three patients, F1 in 20, F2 in 15, F3 in nine, and F4 in four. Among the nine post-sustained virologic response biopsy specimens with moderate-to-severe inflammation (≥A2), four showed S1-to-S3 steatosis (>5% of hepatocytes affected). In the 20 paired biopsy specimens, the inflammation grade significantly regressed ( = 0.0043), but the fibrosis stage did not ( = 0.45). Histological improvement, defined as a ≥ 2-point decrease in the Knodell inflammatory score and no worsening of the fibrosis, was found in 11 (55%) patients. The iron accumulation had significantly regressed ( = 0.0093), but the steatosis had not ( = 0.10).
Even if transaminases become normal after obtaining a sustained virologic response, significant histological inflammation of unknown cause was found in some patients. Additionally, improvement in liver fibrosis was not evident in the short term.
无干扰素的直接抗病毒治疗可使近100%的慢性丙型肝炎病毒感染患者获得持续病毒学应答。
本研究旨在评估慢性丙型肝炎患者在获得直接抗病毒治疗的持续病毒学应答后组织学改善情况。
在691例对直接抗病毒药物获得持续病毒学应答的慢性丙型肝炎患者中,51例在治疗结束后41±20周接受了肝活检,尽管转氨酶水平正常。20例患者有治疗开始前中位数为1.2年时获取的肝活检标本。
在51例接受持续病毒学应答后活检的患者中,炎症分级为A0的有18例,A1的有24例,A2的有8例,A3的有1例;纤维化分期为F0的有3例,F1的有20例,F2的有15例,F3的有9例,F4的有4例。在9例持续病毒学应答后活检标本有中度至重度炎症(≥A2)的患者中,4例显示S1至S3脂肪变性(>5%的肝细胞受累)。在20对配对活检标本中,炎症分级显著改善(P = 0.0043),但纤维化分期未改善(P = 0.45)。组织学改善定义为Knodell炎症评分降低≥2分且纤维化无恶化,11例(55%)患者出现这种情况。铁沉积显著改善(P = 0.0093),但脂肪变性未改善(P = 0.10)。
即使在获得持续病毒学应答后转氨酶恢复正常,仍有部分患者存在原因不明的显著组织学炎症。此外,短期内肝纤维化改善不明显。